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Related Concept Videos

RNA Editing02:23

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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
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Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
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Related Experiment Video

Updated: Aug 25, 2025

Efficient PAM-Less Base Editing for Zebrafish Modeling of Human Genetic Disease with zSpRY-ABE8e
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Engineering a precise adenine base editor with minimal bystander editing.

Liang Chen1, Shun Zhang1, Niannian Xue1

  • 1Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.

Nature Chemical Biology
|October 13, 2022
PubMed
Summary
This summary is machine-generated.

Engineered adenine base editors (ABEs) show improved safety and precision. ABE9 minimizes unwanted edits and off-target effects, enabling efficient generation of disease models in embryos.

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Area of Science:

  • Molecular Biology
  • Gene Editing Technologies
  • Biochemistry

Background:

  • Adenine base editors (ABEs) are powerful tools for A-to-G transitions.
  • Existing ABEs face challenges with bystander mutations and off-target effects, limiting their safety and precision.
  • Development of safer and more accurate base editors is crucial for therapeutic applications and disease modeling.

Purpose of the Study:

  • To engineer novel adenine base editors with reduced bystander and off-target editing.
  • To enhance the precision and efficiency of A-to-G base editing, particularly at homopolymeric adenosine sites.
  • To create improved adenine base editors for generating precise genetic disease models in vivo.

Main Methods:

  • Structure-guided engineering of adenine base editors (ABEs).
  • Introduction of specific mutations (N108Q and L145T) to create ABE8e and ABE9 variants.
  • Assessment of bystander editing, off-target effects (RNA and DNA), and editing precision in mouse and rat embryos.
  • Evaluation of ABE9 performance across a library of guide RNA-target sequence pairs.

Main Results:

  • ABE8e and ABE9 variants demonstrated reduced adenine and cytosine bystander editing compared to previous ABEs.
  • ABE9 exhibited a refined editing window (1-2 nucleotides) with eliminated cytosine editing and minimal RNA off-target effects.
  • ABE9 showed undetectable Cas9-independent DNA off-target effects and high precision (up to 342.5-fold over ABE8e) at homopolymeric adenosine sites.
  • Efficient generation of disease models with desired single A-to-G conversions was achieved in mouse and rat embryos using ABE9.

Conclusions:

  • ABE9 represents a significant advancement in adenine base editor technology, offering enhanced safety and precision.
  • The minimized editing window and reduced off-target activity of ABE9 broaden its potential for precise therapeutic applications and genetic engineering.
  • ABE9 facilitates the accurate correction of pathogenic single-nucleotide variants and the efficient creation of disease models.